The aim of this investigation is to analyze the inflammatory pathways of allograft rejection. Rat experiments will guideline subsequent human studies. We will define (a) which cellular components in different allografts are antigenic, i.e., express transplantation antigens, and (b) which of them are immunogenic, i.e., elicit an immune response, (c) analyze the cellular activation cascade of renal allograft rejection at the site of inflammation and relate the in situ events to changes in the central lymphatic system of the host, (d) investigate how does the host immune response regulate the in situ inflammatory events, (e) define the different cellular and humoral effector mechanisms operative in situ during allograft rejection and (f) investigate how is the inflammation modified by tolerogenic schedules and by drugs with known site(s) of action. These findings will be applied to man by using fine needle aspiration biopsy, transplant aspiration cytology and related cytological methods. We will (g) analyze how is the antigenic anatomy of an allograft modified as a consequence of transplantation, relate these alterations to the immunosuppressive treatment, define how is the inflammatory response modified as a consequence of immuno-suppression, which are the different cellular inflammatory patterns leading to allograft rejection in man and what are the histological correlates of these cytological patterns. Finally, preliminary experiments are made to explore the cellular effector systems operative in human renal transplant rejection. Once the structure of inflammation and the mechanisms regulating the inflammatory response are known it is possible to develop a right strategy to counteract the inflammatory response.